Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats
KPT-335 (Verdinexor) is a novel, orally bioavailable selective inhibitor of nuclear export that has gained significant attention in pharmaceutical research due to its potential anti-tumor and antiviral effects. This study aimed to evaluate the pharmacokinetic parameters and determine the absolute bi...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2025.1576669/full |
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| author | Yuxin Yang Jinyan Meng Zeyu Wen Jianzhong Wang Xingyuan Cao |
| author_facet | Yuxin Yang Jinyan Meng Zeyu Wen Jianzhong Wang Xingyuan Cao |
| author_sort | Yuxin Yang |
| collection | DOAJ |
| description | KPT-335 (Verdinexor) is a novel, orally bioavailable selective inhibitor of nuclear export that has gained significant attention in pharmaceutical research due to its potential anti-tumor and antiviral effects. This study aimed to evaluate the pharmacokinetic parameters and determine the absolute bioavailability of KPT-335 through various administration routes, including oral capsules and tablets, along with intravenous injections. The intravenous group received a dosage of 1 mg/kg body weight (BW), while capsules were administered orally at doses of 0.2, 1, and 2 mg/kg BW. Tablets were also administered orally at 1 and 2 mg/kg BW, with both post-feeding and fasting conditions at the 1 mg/kg BW dosage. Plasma concentrations of KPT-335 were analyzed using ultra-performance liquid chromatography/tandem mass spectrometry. Key pharmacokinetic parameters, including peak concentration (Cmax), area under the curve (AUC0–last), and terminal phase elimination half-life (T1/2), were determined through non-compartmental analysis using WinNonlin 8.1. The absolute bioavailability rates of 43.72, 44.66, and 28.92% for the low, medium, and high-dose capsule groups, respectively. In the tablet formulation, bioavailability at 1 mg/kg BW (fasting), 1 mg/kg BW (feeding), and 2 mg/kg BW (feeding) were 75.92, 70.98, and 47.27%, respectively. KPT-335 demonstrated pharmacokinetic characteristics of rapid absorption and elimination. The results demonstrated that KPT-335 exhibited non-linear pharmacokinetic behavior, indicating that higher doses are not fully absorbed in cats. This finding provides data support for guiding clinical dosing regimens. At the same dose, the absolute bioavailability of the tablet group was higher than that of the capsule group. |
| format | Article |
| id | doaj-art-6e9945a9383e4380a67ddf961de1d0b2 |
| institution | OA Journals |
| issn | 2297-1769 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj-art-6e9945a9383e4380a67ddf961de1d0b22025-08-20T02:36:31ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-05-011210.3389/fvets.2025.15766691576669Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in catsYuxin Yang0Jinyan Meng1Zeyu Wen2Jianzhong Wang3Xingyuan Cao4Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaShanxi Key Lab for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKPT-335 (Verdinexor) is a novel, orally bioavailable selective inhibitor of nuclear export that has gained significant attention in pharmaceutical research due to its potential anti-tumor and antiviral effects. This study aimed to evaluate the pharmacokinetic parameters and determine the absolute bioavailability of KPT-335 through various administration routes, including oral capsules and tablets, along with intravenous injections. The intravenous group received a dosage of 1 mg/kg body weight (BW), while capsules were administered orally at doses of 0.2, 1, and 2 mg/kg BW. Tablets were also administered orally at 1 and 2 mg/kg BW, with both post-feeding and fasting conditions at the 1 mg/kg BW dosage. Plasma concentrations of KPT-335 were analyzed using ultra-performance liquid chromatography/tandem mass spectrometry. Key pharmacokinetic parameters, including peak concentration (Cmax), area under the curve (AUC0–last), and terminal phase elimination half-life (T1/2), were determined through non-compartmental analysis using WinNonlin 8.1. The absolute bioavailability rates of 43.72, 44.66, and 28.92% for the low, medium, and high-dose capsule groups, respectively. In the tablet formulation, bioavailability at 1 mg/kg BW (fasting), 1 mg/kg BW (feeding), and 2 mg/kg BW (feeding) were 75.92, 70.98, and 47.27%, respectively. KPT-335 demonstrated pharmacokinetic characteristics of rapid absorption and elimination. The results demonstrated that KPT-335 exhibited non-linear pharmacokinetic behavior, indicating that higher doses are not fully absorbed in cats. This finding provides data support for guiding clinical dosing regimens. At the same dose, the absolute bioavailability of the tablet group was higher than that of the capsule group.https://www.frontiersin.org/articles/10.3389/fvets.2025.1576669/fullKPT-335pharmacokineticbioavailabilitycatplasma |
| spellingShingle | Yuxin Yang Jinyan Meng Zeyu Wen Jianzhong Wang Xingyuan Cao Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats Frontiers in Veterinary Science KPT-335 pharmacokinetic bioavailability cat plasma |
| title | Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats |
| title_full | Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats |
| title_fullStr | Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats |
| title_full_unstemmed | Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats |
| title_short | Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats |
| title_sort | pharmacokinetic evaluation and bioavailability of kpt 335 verdinexor in cats |
| topic | KPT-335 pharmacokinetic bioavailability cat plasma |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2025.1576669/full |
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